Encore PFO Closure Device - The PerFOrm Trial

This is a prospective, multicenter, randomized clinical study to determine the safety and effectiveness of the Encore PFO closure device, which is indicated for percutaneous, transcatheter closure of a patent foramen ovale (PFO) in patients who have had a cryptogenic stroke due to a presumed paradoxical embolism.

Inclusion criteria

• Diagnosis of PFO, defined as visualization of microbubbles per TEE in the left atrium within three cardiac cycles from the right atrial opacification demonstrating right-to-left shunting at rest and/or during Valsalva release
• Cryptogenic stroke within the last 270 days; stroke is defined as acute focal neurological deficit, presumed to be due to focal ischemia, and confirmed by MRI or CT to be a new, neuroanatomically relevant cerebral infarct

Exclusion criteria

• Age <18 years and age >60 years
• Greater than 50% lumen diameter stenosis of intracranial or extracranial vessels
• Intracardiac thrombus or tumor
• Acute or recent (within 6 months) myocardial infarction (MI) or unstable angina
• Left ventricular aneurysm or akinesis
• Mitral valve stenosis (mitral valve area less than 1.5cm2) or severe mitral regurgitation
• Aortic valve stenosis (gradient >40 mmHg) or severe aortic valve regurgitation
• Mitral or aortic valve vegetation or prosthesis
• Left ventricular ejection fraction <35%
• Other identifiable cause of stroke, including but not limited to aortic arch plaques (protruding >4 mm into the lumen), large artery atherosclerotic disease, an established cardioembolic source, small-vessel occlusive disease, or arterial dissection
• Evidence of a hypercoagulable disorder requiring anticoagulation therapy; this determination will be based on the evaluation of: anticardiolipin antibody (Ab) of the IgG or IgM type, Lupus anticoagulant, B2-glycoprotein-1 Ab, and fasting plasma homocysteine
• Another source of right-to-left shunts identified at baseline, including an atrial septal defect and/or fenestrated septum
• Any history of atrial fibrillation/atrial flutter (chronic or intermittent)
• Active endocarditis or other untreated infections
• Chronic kidney disease stage 4 or higher or end-stage renal failure requiring dialysis (eGFR less than 30)
• Severe liver disease (ALT 3X ULN) or documented cirrhosis
• Lung disease requiring continuous home oxygen
• Uncontrolled hypertension, defined as sustained elevated blood pressure >160/90 mm Hg on medication
• Uncontrolled diabetes mellitus, defined as HbA1c greater than 9 (based on most recent test which must have been collected within the last year)
• Anatomical or physiological structures that do not permit TEE
• Anticipated need for treatment of structural cardiac defects other than PFO
• Concomitant cardiac anomalies requiring an operative procedure
• Hemorrhagic diseases (e.g., coagulopathy, tendency to hemolysis)
• Hypersensitivity to contrast medium or nickel
• Contraindication to aspirin or clopidogrel
• The required sheaths cannot be passed through the relevant vessels for access to the PFO
• Vulnerable patient (e.g., incarcerated or cognitively challenged adults); see Section 7.2.1
• Subject is unable or unwilling to provide informed consent
• Subject is unable to comply with the protocol
• Any other clinical reasons for which the patient would not be an appropriate candidate for the study, as determined by the site investigators